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Accession Number ADA575843
Title Involvement of the Endocannabinoid System in the Development and Treatment of Breast Cancer.
Publication Date Feb 2013
Media Count 11p
Personal Author A. H. Lichtman D. A. Gewirtz S. M. Emery
Abstract Work looking at the interaction of the synthetic cannabinoid WIN55, 212-2 and ionizing radiation has led to preliminary results implicating a novel site of action in the MCF-7 breast cancer model. WIN55,212-2 has been shown previously to dose dependently, and potentially more importantly stereoselectively, inhibit the growth of breast cancer cells. Interestingly, when selective cannabinoid receptor antagonists AM251 and AM630 were administered, we see a failure to antagonize WIN55,212-2 s antiproliferative effects. This despite the observation the MCF-7 cells express mRNA for the cannabinoid receptor CB2, which WIN55,212-2 has been shown to act on in other breast cancer cell lines. Further studies were conducted that pharmacologically excluded the involvement of members of the PPAR receptor system, known to be reactive to WIN55,212-2. TRPV1 is reported to be sensitive to some cannabinoids as well, and subsequently was evaluated and then excluded based on similar pharmacological experiments. Studies from a colleague have implicated the involvement of sphingosine-1-phosphate receptors as a potential site of action for WIN55,212-2 in the brain. Our work has since shown WIN55,212-2 to be able to antagonize this sphingosine-1-phosphate receptor system, and it s known importance to MCF-7 cell growth gives a potential mechanism of action. This interaction has not previously been reported and suggests a novel site of action that could be exploited with future research.
Keywords Breast cancer
Cannabinoid receptors
Ionizing radiation
Neuromodulatory lipids
Neuromodulatory receptors
Synthetic cannabinoid win552122

Source Agency Non Paid ADAS
NTIS Subject Category 57C - Botany
57Z - Zoology
57A - Anatomy
57S - Physiology
57E - Clinical Medicine
Corporate Author Virginia Commonwealth Univ., Richmond.
Document Type Technical report
Title Note Annual rept. 15 Jan 2012 - 14 Jan 2013.
NTIS Issue Number 1319
Contract Number W81XWH-11-1-0163

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